Is CHM p.Ser28Ala (c.82T>G) pathogenic?

CHM p.Ser28Ala (c.82T>G) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.0835); Very rare (popmax 0.00296%, eas); Associated with inherited retinal dystrophy.

What condition is associated with CHM p.Ser28Ala (c.82T>G)?

CHM p.Ser28Ala (c.82T>G) is associated with inherited retinal dystrophy (ClinVar).

How common is CHM p.Ser28Ala (c.82T>G) in the general population?

CHM p.Ser28Ala (c.82T>G) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about CHM p.Ser28Ala (c.82T>G)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

CHM p.Ser28Ala

c.82T>G · rs184699911 · VCV3028626

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.296	indeterminate
SaProt	LLR -4.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	18.28	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,729 alleles

Overall 0.000896% 1/111,578 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHM
Protein: p.Ser28Ala
Coding: c.82T>G
MANE Select: NM_000390
dbSNP: rs184699911
Type: single nucleotide variant
Location: chrX:86027525 (GRCh38)
Structure: AlphaFold pLDDT 81.05

Full CHM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHM p.Ser28Ter Likely pathogenic ★ same residue
CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.1244+1G>A Pathogenic ★★ same condition
CHM c.189+1G>A Pathogenic ★★ same condition
CHM c.49+5G>A Pathogenic/Likely pathogenic ★★ same condition
CHM c.940+1G>A Pathogenic ★★ same condition
CHM p.Arg239Ter Pathogenic ★★ same condition
CHM p.Arg253Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chm-p-ser28ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown